The goal of this project is to determine the mechanisms responsible for decline in immune function in advanced age in man. The emphasis is on defining age-associated changes in the expression and synthesis of a variety of cellular proteins in various types of immunologically important cells and determining the impact of these changes on cell function. Changes in the expression of at least some proteins were suggestive of an accumulation of less mature T cells in advanced age, presumably due to loss of thymic function. The objective is to determine if these changes point to this or a variety of underlying mechanisms for depressed immune function. The aims are: 1) Isolate and characterize the cell types with changes suggestive of less differentiated T cells and determine if abnormal expression of other proteins occurs in these cells. 2) Determine the extent to which increase in these cell types is associated with depressed in vivo immune function and with clinical features of advanced age. 3) Determine the extent to which advanced age affects the synthesis and expression of proteins unrelated to differentiation in different cell types with emphasis on explaining individual variation in protein synthesis in old volunteers and increase histone specific proteolysis. 4) Determine the in vitro functional significance of changes in synthesis and expression of mononuclear cell proteins in advanced age. Methods used to achieve these aims include: determination of T cell associated surface marker and cell purification based on monoclonal antibodies, measurement of in vivo immune function by skin test reactions to tuberculin, determination of protein expression and synthesis by gel electrophoresis and uptake of radiolabeled amino acids, and measurement of function by kinetics of mitogen induced proliferation and aggregation, cell adhesion and motility. The results are expected to contribute not only to understanding of the mechanisms that lead to decreased immune function in the elderly, but to understanding of the role of various proteins in the function of normal cell types in the immune response.